EFFICACY OF TUMOR-CELL VACCINE AFTER INCORPORATING MONOPHOSPHORYL LIPID-A (MPL) IN TUMOR-CELL MEMBRANES CONTAINING TURNER-ASSOCIATED GANGLIOSIDE

Murine B16 melanoma expresses the ganglioside GM(3). GM(3) shed from t umor cells is immunosuppressive and promotes tumor growth(1). Reductio n or elimination of the shed GM(3) could be therapeutic, and the anti- GM(3) antibodies may reduce and clear the shed ganglioside. To test th is hypothesis, mice were challenged with tumor cells, with or without inducing anti-GM(3) antibody response. Since gangliosides are poor imm unogens and T-cell independent antigens, an adjuvant (monophosphoryl l ipid A (MPL), a non-toxic lipid A of Salmonella), directed against B-c ells, was employed. MPL was incorporated onto liposomes and into the s urface membrane of B16 mouse melanoma cells; both are rich in GM(3). C 57BL/6J mice immunized with MPL-liposomes or MPL-B16 cells responded w ith elevated levels of anti-GM(3) IgM. Non-immunized mice or mice immu nized with B16 cells alone or ganglioside GM(3) alone (without MPL) el icited poor anti-GM(3) IgM response, confirming the GM(3)'s immunologi c crypticity and MPL's immunopotentiating effect. MPL's immunopotentia ting effect was improved by coupling it to melanoma cell membranes. C5 7BL/6J mice were immunized with irradiated B16 alone or MPL alone or M PL-conjugated irradiated B16. After three weekly immunizations, each m ouse received a challenge dose of viable syngeneic B16. Neither MPL al one nor B16 alone had a significant effect on tumor growth or host sur vival; however, administration of MPL-conjugated B16 cells significant ly prevented tumor growth and prolonged survival. Our results indicate that MPL-incorporated B16 cells augment the anti-GM(3) IgM response, which may reverse GM(3)-induced immunosuppression by eliminating tumor -derived GM(3), and restore immunocompetence.